Efficient strategy for detecting gene x gene joint action and its application in schizophrenia

Won, Sungho and Kwon, Min-Seok and Mattheisen, Manuel and Park, Suyeon and Park, Changsoon and Kihara, Daisuke and Cichon, Sven and Ophoff, Roel and Nöthen, Markus M. and Rietschel, Marcella and Baur, Max and Uitterlinden, Andre G. and Hofmann, A. and Group Investigators, and Lange, Christoph. (2014) Efficient strategy for detecting gene x gene joint action and its application in schizophrenia. Genetic Epidemiology, 38 (1). pp. 60-71.

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Official URL: https://edoc.unibas.ch/61593/

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We propose a new approach to detect gene x gene joint action in genome-wide association studies (GWASs) for case-control designs. This approach offers an exhaustive search for all two-way joint action (including, as a special case, single gene action) that is computationally feasible at the genome-wide level and has reasonable statistical power under most genetic models. We found that the presence of any gene x gene joint action may imply differences in three types of genetic components: the minor allele frequencies and the amounts of Hardy-Weinberg disequilibrium may differ between cases and controls, and between the two genetic loci the degree of linkage disequilibrium may differ between cases and controls. Using Fisher's method, it is possible to combine the different sources of genetic information in an overall test for detecting gene x gene joint action. The proposed statistical analysis is efficient and its simplicity makes it applicable to GWASs. In the current study, we applied the proposed approach to a GWAS on schizophrenia and found several potential gene x gene interactions. Our application illustrates the practical advantage of the proposed method.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Dec 2020 10:15
Deposited On:16 Dec 2020 10:15

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